PROJECT SUMMARY HIV drug resistance (HIVDR) is a threat to the success of antiretroviral therapy (ART) and a major barrier to the elimination of AIDS as a public health problem. Persons with HIV who develop virological failure during ART are at high risk of developing HIVDR and possibly transmitting a drug-resistant strain to others, and persons who are infected with a drug-resistant HIV strain are at high risk of developing virological failure. Comprehensive, accurate, and publicly available HIVDR data are essential for population-based monitoring of acquired and transmitted HIVDR, for the clinical management of HIV-infected patients, and for identifying overall drug-development needs. A public database that curates, annotates, and disseminates the primary data from HIVDR studies will make it possible to identify and characterize the HIVDR mutations most relevant to surveillance, clinical management, and drug development, and it will expedite research into the mechanisms of HIVDR and the predictors of response to the newest ARV regimens. The Stanford HIV Drug Resistance Database (HIVDB) has provided a unique conceptual framework for addressing data-intensive questions about the main molecular targets of HIV therapy: reverse transcriptase, protease, and integrase. HIVDB?s sequence analysis programs have also become integrated into the workflows of many research laboratories worldwide. This Research Resource project is designed to improve HIVDB by (i) replacing the previous ad hoc approach to data recruitment with a sustainable systematized approach; (ii) streamlining and automating many of its core functions; (iii) expanding the user base to target the most pressing global HIVDR research questions; and (iv) establishing principles of governance for the inclusion of data in HIVDB and access to data in HIVDB. Specific Aims: (1) To create a sustainable resource that catalogs the extent and genetic mechanisms of acquired and transmitted HIVDR. Accomplishing this aim will enable researchers to identify gaps in the published literature, perform novel analyses, and discover new knowledge; (2) To regularly update the knowledge base required for interpreting HIV genotypic resistance tests and other online HIVDR analyses. Accomplishing this aim will establish standards that can be applied to the analysis of HIVDR data across the many molecular epidemiological and clinical studies performed each year; and (3) To provide enhanced support for national and international research collaborations by creating improved software clients and APIs for accessing HIVDB and new open-source software for analyzing HIVDR data. Accomplishing this aim will support researchers in using HIVDB to advance their research, promote public availability of data from new HIVDR studies, and generate feedback to be used in developing additional HIVDR research tools.